Previous studies in our laboratory have shown that selenium can inhibit the growth of various transplantable tumor cell lines. Recent studies also show that differences in susceptibility of canine mammary tumor cells to selenium do occur. We, therefore, capitalize on our prior experience with comparative studies using normal and neoplastic mammary cells to address the effects of selenium of cellular proliferation. These studies will aid in determining what factors are most important in determining which malignant cells will be sensitive to selenium supplementation under physiological circumstances. To address these factors that modify cellular susceptibility to selenium, studies will be conducted to determine the uptake and distribution of selenium in a sensitive and relative insensitive mammary tumor cell and compare these results with data from a non-neoplastic short-term culture. These studies will determine if differences in the normal route of selenium detoxification account for cellular sensitivity to selenium. Therefore, the fomation of dimethylselenide will be monitored as a function of selenium exposure to normal and neoplastic mammary cells. Since differences in the ability of selenium to alter key metabolic pathways may be a contributing factor in cellular tolerance, the biochemical effects of selenium supplementation will be addressed. Alterations in the interconversion of disulfide and sulfhydryl groups in protein or other biologically active compounds may explain the antitumorigenic properties of selenium. Therefore, disulfide reduction will be examined as a function of selenium exposure in both non-neoplastic and neoplastic canine mammary cells. A thorough understanding of the influence of the selenium on normal and neoplastic tissue is essential before well controlled clinical trials in humans are initiated.